The ability to non-invasively image internal body structures and diseased tissues within a patient's body is an extremely important diagnostic tool in the practice of modern medicine. Among such non-invasive imaging techniques include magnetic resonance imaging (MRI), x-ray imaging, ultrasonic imaging, x-ray computed tomography, emission tomography, and others. Magnetic resonance imaging can provide two-dimensional cross-sectional images through a patient, providing color or gray scale contrast images of a portion of the body. These two-dimensional images can then be reconstructed to provide a 3-dimensional image of a portion of the body. MRI is advantageous, inter alia, because it does not expose the patient or medical practitioner to harmful radiation and can provide detailed images of the observed area. These detailed images are valuable diagnostic aids to medical practitioners and can be used to devise, monitor or alter a treatment approach.
Magnetic resonance imaging (MRI) produces images by differentiating detectable magnetic species in the portion of the body being imaged. In the case of 1H MRI, the detectable species are protons (hydrogen nuclei) that possess an inherent spin magnetic moment such that these protons behave like tiny magnets. Images are obtained by placing the patient or area of interest within a powerful, highly uniform, static magnetic field. The protons in the area of interest align like tiny magnets in this field. Radiofrequency pulses are then utilized to create an oscillating magnetic field perpendicular to the main field, from which the nuclei absorb energy and move out of alignment with the static field, in a state of excitation. As the nuclei return from excitation to the equilibrium or relaxed state, a signal induced in the receiver coil of the instrument by the nuclear magnetization can then be transformed by a series of algorithms into diagnostic images. Images based on different tissue characteristics can be obtained by varying the number and sequence of pulsed radiofrequency fields in order to take advantage of magnetic relaxation properties of the detectable protons in the area of interest.
The environment of the detectable protons alters the magnetic properties thereof such that different field strengths and pulsation frequencies affect the ability of the MRI device to detect such protons and differentiate them from other protons in the surrounding environment. In order to obtain good images, MRI relies upon the differentiation of such protons to provide contrast between the area of interest and the surrounding environment. For example, diseased or damaged tissue may result in a sufficiently different environment for the detectable protons therein relative to that of protons in the surrounding environment. Sufficient contrast is thereby provided by the inherently different environments to produce a good image of the area of interest.
However, in order to enhance the differentiation of detectable species in the area of interest from those in the surrounding environment, contrast agents are often employed. These agents alter the magnetic environment of the detectable protons in the area of interest relative to that of protons in the surrounding environment and, thereby, allow for enhanced contrast and better images of the area of interest.
Contrast agents thus function to alter the signal intensity arising from detectable protons from that arising from detectable protons in the surrounding environment, thereby differentiating the area of interest from the surrounding environment. Nearly all of the classes of contrast agents create their desired effect by changing the spin-lattice relaxation time (T1) and/or the spin-spin relaxation time (T2) of the detectable protons. Those contrast agents that operate predominantly on spin-spin relaxation times are the superparamagnets, such as particulate iron oxides. Those contrast agents that operate predominantly on the spin-lattice relaxation time are the paramagnets. These species possess unpaired electrons and thus have a net magnetic moment. It is the magnetic moment of the contrast agent that leads to an increase in the spin-lattice relaxation rate of detectable protons, thereby differentiating these protons from those in the surrounding environment. For contrast-enhanced MRI it is desirable that the contrast agent have a large magnetic moment, with a relatively long electronic relaxation time. Based upon these criteria, contrast agents such as Gd(III), Mn(II) and Fe(III) have been employed. Gadolinium(III) has the largest magnetic moment among these three and is, therefore, a widely-used paramagnetic species to enhance contrast in MRI. Chelates of paramagnetic ions such as Gd-DTPA (gadolinium ion chelated with the ligand diethylenetriaminepentaacetic acid) have been employed as MRI contrast agents. Chelation of the gadolinium or other paramagnetic ion is believed to reduce the toxicity of the paramagnetic metal by rendering it more biocompatible, and can assist in localizing the distribution of the contrast agent to the area of interest.
Implantable or insertable medical devices such as catheters, guidewires, balloons, stents, and a variety of other implantable or insertable medical devices are conventionally used to both diagnose and treat medical conditions. To maximize the effectiveness of such medical devices, it is commonly desirable to both properly position the device within a patient and thereafter ascertain the precise location of such device upon implantation or insertion thereof.
In recent years, there has been a trend to use MRI as a tracking/guiding tool for monitoring interventional procedures using an implantable or insertable medical device or as a tool to determine the position of the device upon implantation or insertion thereof. The ability of MI to produce extremely detailed images of an area of interest, and the minimization of harmful radiation exposure to the patient or medical practitioner of radiation attendant to the use of X-ray imaging, are distinct advantages of MRI over other imaging techniques. To this end, MRI has been used with varying degrees of success to assist in the placement of a medical device and/or to determine the position of a medical device upon insertion or implantation. Unfortunately, most implantable or insertable medical devices are composed of materials such as organic polymers, metals, ceramics, or composites thereof, which do not produce adequate signals for detection by MRI techniques. Therefore, the effectiveness of MRI to monitor the insertion of such devices and the position thereof after insertion or implantation has been limited.
It would, therefore, be desirable to provide implantable or insertable medical devices that are visible under MRI. For example, it has been proposed in U.S. Pat. No. 5,154,179 to incorporate MRI contrast enhancing agents such as ferromagnetic particles within the polymeric material used to construct catheters. This patent discloses incorporation of ferromagnetic particles such as iron and iron oxides during the extrusion of the plastic to form the catheter. The embedded ferromagnetic particles are disclosed to make the catheter visible under MRI by providing contrast with respect to the surrounding body tissues. The direct incorporation of ferromagnetic or paramagnetic materials into the polymeric material of catheters and other implantable or insertable medical devices, however, suffers from numerous drawbacks. For example, in order to provide enhanced contrast under MRI, paramagnetic materials, such as paramagnetic ions, require the proximity of water or another proton-bearing substance. It is difficult to incorporate such substances during the shaping of the polymeric materials used to construct the medical device. For example, water associated with hydrated paramagnetic ions can be readily lost during high temperature extrusion of the polymeric material used to construct the medical device. Moreover, the incorporation of such ferromagnetic or paramagnetic materials can detrimentally affect the requisite mechanical properties, such as strength and flexibility, of the polymeric materials used to construct the implantable or insertable medical device.
U.S. Pat. No. 5,154,179 also discloses introduction of a liquid or gel contrast agent containing a paramagnetic material into a catheter lumen. The paramagnetic material is disclosed to provide contrast with respect to surrounding body tissues to render the catheter visible under MRI. The incorporation of a liquid or gel in the catheter is difficult from a manufacturing view, limits the flexibility of the catheter, and is generally inconvenient.
U.S. Pat. No. 5,817,017 discloses the incorporation of paramagnetic ionic particles into non-metallic materials used to construct catheters and other medical devices to provide such devices with enhanced visibility under MRI. The paramagnetic ionic particles comprise paramagnetic ions incorporated with water or other proton-donating fluid into carrier particles such as zeolites, molecular sieves, clays, synthetic ion exchange resins and microcapsules. This patent discloses that the paramagnetic ionic particles can be combined with suitable polymeric materials and extruded into a desired shape, such as a flexible tube. This patent further discloses that extrusion of polymeric materials incorporating such paramagnetic ionic particles can be conducted without substantial loss of the proton-donating fluid, which is essential for image enhancement using the paramagnetic metals. Among paramagnetic ions that can be incorporated into the carrier particles are mentioned trivalent gadolinium. Among proton-donating fluids that can be incorporated with the paramagnetic ions in the carrier particles, are water, alcohols such as glycerols (e.g., propylene glycol, polyethylene glycol and ethylene glycol), detergents such as sulfonated compounds, ethers such as glyme and diglyme, amines, imidazoles, and Tris.
Despite these and other attempts to render implantable or insertable medical devices visible under MRI, there remains a need for a simplified, cost-effective approach that avoids the disadvantages of the methods discussed above.
The present invention is, therefore, directed to implantable or insertable medical devices adapted to be visible under magnetic resonance imaging (MRI). More particularly, the present invention is directed to medical devices provided with a coating adapted to render the medical device visible under MRI; the use of such medical devices in a medical procedure during or after which the position of the medical device can be viewed by MRI; and, the use of coatings adapted to render medical devices coated therewith visible under MRI.